Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of femoral atheroma after 1 year of treatment with diet and nicotinic acid plus fenofibrate was studied in 45 asymptomatic, hyperlipidaemic, middle-aged male subjects in a non-randomized controlled study. The median serum very low density lipoprotein (VLDL) cholesterol concentration and the low density lipoprotein (LDL) cholesterol concentration were lowered by 67% and 36%, respectively, in the treatment group. The median serum high density lipoprotein (HDL) cholesterol concentration was increased by 23%. Femoral atheroma was estimated by overall atherosclerosis score (OAS). Changes in femoral atherosclerosis were estimated by intrapair comparison of angiograms. Progression was found in 24% and 40% in the treatment and control groups, respectively. Regression occurred in 29% and 0%, respectively. The OAS decrease correlated with reductions in VLDL cholesterol and systolic blood pressure.
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PMID:The effect of serum lipid regulation on the development of femoral atherosclerosis in hyperlipidaemia: a non-randomized controlled study. 235 25

Patients with heterozygous familial hypercholesterolemia (FH) constitute a unique population at high risk for the premature development of coronary artery disease (CAD) and in whom long-term hypocholesterolemic therapy to reduce elevated levels of low density lipoprotein (LDL) cholesterol is most clearly indicated. Optimal therapy invariably requires diet regulation plus hypolipidemic drug therapy. When used as single agents, the bile-acid sequestrants, cholestyramine and colestipol, lower LDL cholesterol concentrations by 20% to 35% in compliant patients, whereas decreases of 20% to 30% can be achieved with nicotinic acid in doses of 3 to 6 g/day. Bezafibrate, fenofibrate, and ciprofibrate have also been shown to lower LDL cholesterol levels by 20% to 30%, and these drugs are more effective than gemfibrozil and clofibrate. Probucol, neomycin, and D-thyroxine reduce LDL cholesterol concentrations by 10% to 15% in single-drug use. Clinical trials with a new class of drugs that inhibit the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, and that includes lovastatin, simvastatin, and pravastatin indicate that these drugs lower LDL cholesterol concentrations by 30% to 50% in patients with heterozygous FH. Combined drug therapy with a bile-acid sequestrant and nicotinic acid lowers LDL cholesterol by 40% to 55%, whereas fenofibrate, bezafibrate, or probucol plus a bile-acid sequestrant results in reductions varying from 25% to 50%. The combinations of an HMG CoA reductase inhibitor with either a bile-acid sequestrant or nicotinic acid appears to be the most promising, and these regimens reduce LDL cholesterol levels by 45% to 60%. With appropriate use, the currently available hypocholesterolemic drugs have the potential to markedly change the natural history of premature atherosclerosis that occurs in untreated patients with FH.
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PMID:Treatment of heterozygous familial hypercholesterolemia with lipid-lowering drugs. 249 89

The results of the World Health Organization Cooperative Trial, the Coronary Drug Project, the Coronary Primary Prevention Trial and the Helsinki Heart Study indicate that clinical expression of coronary artery disease can be delayed with pharmacologic modification of plasma lipoproteins. Change in coronary artery disease can be semiquantitated by repeat arteriograms. Three randomized clinical trials indicate that rate of progression of atherosclerosis, as defined by arteriography, can be reduced, and existing lumen obstruction decreased. Tendon xanthomas occur in hypercholesterolemia, and reduction in xanthoma size with drug therapy suggests an improved atherosclerotic disease state. The clinician has a variety of pharmacologic therapies available. The role of bile acid-binding resins, fibric acid derivatives, hydroxymethylglutaryl coenzyme A reductase inhibitors, nicotinic acid and antioxidants is each unique. Understanding the role of lipoproteins in atherosclerosis will help in selecting the most appropriate therapy for each individual patient. Medications not designed for their lipoprotein effects can significantly alter lipoproteins. Medications, such as nonselective beta blockers, can alter low-density lipoprotein (LDL) subclass distribution with no change in LDL cholesterol content. Such changes may eradicate part of the beneficial cardiovascular effect of beta blockade therapy. In the future, therapeutic choices may depend in part on lipoprotein abnormalities such as lipoprotein (a), apolipoprotein E isoforms, hyperapobetalipoproteinemia, LDL.
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PMID:Drug therapy and the prevention of atherosclerosis in humans. 267 29

There are indications that treatment of hypercholesterolemia by means of drugs reduce risk of atherosclerosis in patients with increased concentrations of atherogenic lipoproteins. Such therapy should be initiated only after satisfactory exclusion of secondary causes of hyperlipoproteinemia, and should be regarded as an adjunct to appropriate dietary therapy. Drug therapy should be strongly considered in patients with total cholesterol above 8-9 mmol/l on diet therapy only. Drug therapy should be considered at even lower concentrations of cholesterol when coronary heart disease is present and in familial forms of hyperlipidemia when increased risk of atherosclerosis has been documented. In patients with increased plasma concentrations of total cholesterol the drugs of choice are agents which enhance the rate of LDL catabolism (resins) or reduce the rate of LDL synthesis (nicotinic acid). Fibrates should be used when triglycerides and cholesterol are both increased. HMG CoA reductase inhibitors offer considerable promise in the therapy of patients with primary hypercholesterolemia. Probucol may be used in combination with other drugs, particularly when xanthomas are present in patients with familial hypercholesterolemia.
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PMID:[Drug therapy of hypercholesterolemia. Treatment of hypercholesterolemia in adults--a Norwegian therapeutic program 1988]. 270 70

The article analyses the immediate results of preoperative management and treatment of 13 patients with atherosclerosis obliterans of the lower limbs on the basis of drug hypolipidemic therapy and hemosorption on nonspecific sorbents of type CKH. Drug therapy comprised nicotinic acid, its derivatives in a daily dose of up to 2.5 mg, cholestiramine up to 20 g daily, vitamin therapy, and prodectin. Hemosorption was conducted on CKH-2K once in 4 days; 7 patients were given 5 perfusions each, 6 patients--7 perfusions each. Considerable clinical improvement occurred, hemodynamics improved, improvement of lipid metabolism was manifested by decrease of total cholesterol by 22%, triglycerides by 10%, and low density lipoproteins by 43% and increase of high density lipoproteins by 100%. The Cch atherogenicity coefficient decreased by 41%. The expediency of conducting no more than 4 sorptions was revealed and substantiated. Reconstructive vascular operations were performed on the patients. The postoperative period was uneventful. The late-term postoperative period was marked by progressive improvement of rheographic and biochemical values and stable normalization of lipid metabolism.
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PMID:[Preoperative preparation of patients with arteriosclerosis obliterans]. 272 47

The pathogenesis of atherosclerosis is a multifactorial process. A possible anti-atherosclerotic drug should therefore interfere with different targets that are important during the development of an atherosclerotic lesion. Two of the early events are the activated migration and proliferation of arterial smooth muscle cells. Here we investigated in several in vivo and in vitro experiments the effect of two nicotinic acid derivatives L44 and L44-0, on smooth muscle cell migration and proliferation. Balloon catheter de-endothelialization was used as an animal model for intimal lesion formation. Migration was subsequently quantified in vitro using the explant outgrowth technique. Subcultured smooth muscle and endothelial cells were used to test the effect of the drugs on proliferation. Time-lapse video microscopy was applied to differentiate between smooth muscle cell migration and proliferation on the level of individual cells. We showed that L44 and L44-0 are very effective in decreasing smooth muscle cell proliferation and migration. Endothelial cell proliferation, important to re-establish endothelial integrity was, however, not affected.
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PMID:Differential effect of nicotinic acid derivatives on smooth muscle and endothelial cell proliferation. 276 60

High-density lipoprotein (HDL) cholesterol, an independent coronary heart disease (CHD) risk factor, is inversely associated with CHD. Whether interventions to increase concentrations of HDL--particularly the HDL2, HDL3, and apolipoprotein A1 subfractions--will reduce the incidence of CHD in high-risk patients is thus an area of intense speculation. Both nonpharmacologic and pharmacologic regimens will raise HDL concentrations. Nonpharmacologic approaches include habitual high-level aerobic exercise and weight loss--both of these somewhat more effective in men than in women--cessation of cigarette smoking, and changing of dietary habits. A number of drugs have been found to elevate HDL cholesterol. These include the bile acid-binding resin cholestyramine, nicotinic acid, gemfibrozil, phenytoin, exogenous estrogens, and alcohol. Terbutaline has also been reported to raise HDL cholesterol. It is not yet known whether, and to what degree, pharmacologic and nonpharmacologic elevation of HDL cholesterol will retard or reverse the progression of atherosclerosis. Conversely, HDL cholesterol is lowered by a broad variety of drugs, including anabolic--androgenic steroids, exogenous progestins, and probucol, which are used therapeutically to reduce low-density lipoprotein (LDL) cholesterol. Some agents used to treat hypertension also reduce HDL cholesterol, especially thiazide diuretics and the beta blockers, with the possible exception of pindolol. In the antiadrenergic class of antihypertensive agents, reserpine and methyldopa lower HDL cholesterol, but the alpha blocker prazosin does not appear to affect HDL cholesterol. The alpha agonist guanabenz has no effect on HDL cholesterol, and the vasodilator carprazidil has been reported to raise HDL cholesterol. In light of these facts, investigations should be undertaken to determine whether the metabolic effects of antihypertensive agents blunt their beneficial effects on CHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonpharmacologic and pharmacologic alteration of high-density lipoprotein cholesterol: therapeutic approaches to prevention of atherosclerosis. 286 87

Following the recent demonstration that both cholestyramine and nicotinic acid decrease mortality from coronary heart disease, there is a new enthusiasm for hypolipidaemic therapy. The agents in current use are, however, insufficiently active or are accompanied by unacceptable side effects. An understanding of the mode of action is necessary, both to optimize treatment guidelines (e.g. regarding combination therapy or use in specific subsets of patients) and to develop new agents with preferred actions on rate-limiting steps. A reduction in LDL cholesterol concentration remains the principal desired action, although an elevation in HDL may also be beneficial. The main categories of commercially available agent comprise the anion exchange resins (inhibitors of bile acid absorption); cholesterol absorption inhibitors; fibrates (probably acting by enhancing lipoprotein lipase); and probucol (affecting LDL clearance). The most interesting of the new agents in clinical trials are the beta-hydroxy-beta-methylglutaryl-CoA reductase inhibitors, but other types of agent are at an earlier stage of evaluation, e.g. acyl-CoA: cholesterol acyltransferase inhibitors and peptide cofactors. It is not yet certain whether all the approaches to cholesterol lowering have equal validity, although an effect on biological endpoints is obtained for a variety of agents. Future evaluation will be aided by the implementation of noninvasive methods to quantify atherosclerosis and by the use of simple, 'dry-chemistry', cholesterol assays to screen populations.
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PMID:Mode of action of lipid-lowering drugs. 289 41

The antiatherosclerotic profile of nicotinic acid and of its new water-insoluble derivative was studied in an 8-day experiment in rats. Both drugs lowered plasma triglyceride levels significantly, while other lipoprotein parameters were unaffected. Circulating immune complex levels were decreased with lysosomal membrane permeability by both drugs. Glunicate proved to be a powerful antioxidant with regard to enzymatic lipid peroxidation when studied in the liver microsomal system. The relevance of these findings to the antiatherosclerotic effect of the drugs and the biological significance of antioxidant treatment is discussed. On the basis of these data glunicate seems to be a promising new therapeutic tool against atherosclerosis and merits further study.
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PMID:Hypolipaemic effect and inhibition of lipid peroxidation by glunicate in rats on atherogenic diet. 294 Dec 65

The rationale for drug treatment of patients with hypercholesterolemia is that sustained reductions in the plasma concentrations of atherogenic lipoproteins will retard the development of atherosclerosis. Drug therapy should be initiated only after the exclusion of secondary factors and after an adequate trial of dietary therapy has failed to lower plasma cholesterol to a satisfactory level. The bile-acid sequestrants (cholestyramine and colestipol), nicotinic acid, and lovastatin are the most effective drugs for use in patients with primary hypercholesterolemia; these agents reduce total and LDL cholesterol concentrations by 15-35%. For patients with high concentrations of LDL cholesterol who concurrently have hypertriglyceridemia, nicotinic acid is the drug of choice, and bile-acid sequestrants are contraindicated. Combined therapy with drugs that have different mechanisms of action can be effectively utilized in the treatment of patients with severe hypercholesterolemia; combinations involving lovastatin, nicotinic acid, and bile-acid sequestrants are the most effective.
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PMID:Drug therapy of hypercholesterolemia. 304 95


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